| Title: | The genetic architecture of multimodal human brain age |
| Journal: | Nature Communications |
| Published: | 23 Mar 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38521789/ |
| DOI: | https://doi.org/10.1038/s41467-024-46796-6 |
| URL: | https://www.nature.com/articles/s41467-024-46796-6.pdf |
Publication 10063
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Abstract
The complex biological mechanisms underlying human brain aging remain incompletely understood. This study investigated the genetic architecture of three brain age gaps (BAG) derived from gray matter volume (GM-BAG), white matter microstructure (WM-BAG), and functional connectivity (FC-BAG). We identified sixteen genomic loci that reached genome-wide significance (P-value < 5×10−8). A gene-drug-disease network highlighted genes linked to GM-BAG for treating neurodegenerative and neuropsychiatric disorders and WM-BAG genes for cancer therapy. GM-BAG displayed the most pronounced heritability enrichment in genetic variants within conserved regions. Oligodendrocytes and astrocytes, but not neurons, exhibited notable heritability enrichment in WM and FC-BAG, respectively. Mendelian randomization identified potential causal effects of several chronic diseases on brain aging, such as type 2 diabetes on GM-BAG and AD on WM-BAG. Our results provide insights into the genetics of human brain aging, with clinical implications for potential lifestyle and therapeutic interventions. All results are publicly available at https://labs.loni.usc.edu/medicine.</p>
18 Authors
- Junhao Wen
- Bingxin Zhao
- Zhijian Yang
- Guray Erus
- Ioanna Skampardoni
- Elizabeth Mamourian
- Yuhan Cui
- Gyujoon Hwang
- Jingxuan Bao
- Aleix Boquet-Pujadas
- Zhen Zhou
- Yogasudha Veturi
- Marylyn D. Ritchie
- Haochang Shou
- Paul M. Thompson
- Li Shen
- Arthur W. Toga
- Christos Davatzikos
1 Application
| Application ID | Title |
|---|---|
| 35148 | iSTAGING (Imaging-based coordinate SysTem for AGing and NeurodeGenerative diseases) |
Enabling scientific discoveries that improve human health